We recently determined that continual administration of low doses of the antiprogestin ZK 137 316 (Schering AG) to female rhesus monkeys permits ovarian/menstrual cyclicity, but disrupts endometrial growth and morphology. The current study tested the contraceptive efficacy of this low dose antiprogestin regimen. Thirty adult females received daily IM injections (n=10/group) of vehicle (controls), 0.01 mg or 0.03 mg ZK 137 316/kg body weight for 30 days prior to and during continual cohabitation with males of proven fertility in cages designed to house a breeding pair. Females were checked daily for menses. Mating between pairs was confirmed by visual observation and evidence of sperm after vaginal swabs. Ultrasounds were performed when pregnancy was suspected based on menstrual records. Treatment continued until confirmation of pregnancy or for up to 5 consecutive months after pairing. After 4 months of paired housing, a cumulative pregnancy rate of 90% (9/10) was observed in controls. In contrast, only 3/10 females receiving 0.01 mg/kg became pregnant, with conception occurring within the first 2 months of paired housing. No pregnancies were observed in the 0.03 mg/kg group. All 7 of the remaining nonpregnant animals receiving 0.01 mg/kg, but only 6/10 in the 0.03 mg/kg group, exhibited timely menses throughout antiprogestin treatment. Mating and vaginal sperm were evident in all animals. Toxicologic studies of nonpregnant females following 5 consecutive months of antiprogestin treatment are ongoing. Thus, a chronic regimen of low dose ZK 137 316 that permits continued ovarian/menstrual cyclicity prevents pregnancy in a nonhuman primate model. Although the 0.01 mg/kg dose was contraceptive in the majority of females, it was initially less effective than the 0.03 mg/kg dose. This novel regimen of antiprogestin treatment can be considered as a potential contraceptive in women.